INSERM UMR-1178, CESP, Faculté de Médecine Paris-Sud, Paris-Saclay University, Le Kremlin Bicêtre, France.
Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Psychiatry Clin Neurosci. 2020 Feb;74(2):112-117. doi: 10.1111/pcn.12944. Epub 2019 Nov 2.
Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressed patients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC).
Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5-hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3-hydroxyanthranilic acid).
Sixty (34.7%) patients were antidepressant-drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5-hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5-hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients.
Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.
色氨酸是外周和中枢产生的 5-羟色胺和犬尿氨酸的唯一前体。在抑郁症患者中，色氨酸、5-羟色胺、犬尿氨酸及其代谢物水平仍不清楚。因此，本研究广泛研究了 173 例患有当前重度抑郁发作（MDE）的患者和 214 例健康对照者（HC）的外周色氨酸和 5-羟色胺和犬尿氨酸代谢物。
定量检测 11 种外周代谢产物的空腹血浆水平：色氨酸、5-羟色胺途径（5-羟色胺、其前体 5-羟色氨酸和其代谢产物 5-羟吲哚乙酸）和犬尿氨酸途径（犬尿氨酸和其六种代谢产物：邻氨基苯甲酸、犬尿氨酸、烟酰胺、烟酸、黄尿酸和 3-羟基犬尿氨酸）。
60 例（34.7%）患者未服用抗抑郁药。MDE 患者与 HC 患者的色氨酸水平无差异。MDE 患者的 5-羟色胺及其前体（5-羟色氨酸）水平低于 HC，而其代谢产物（5-羟吲哚乙酸）水平在标准范围内。MDE 患者的犬尿氨酸和四种代谢产物（犬尿氨酸、烟酰胺、烟酸和黄尿酸）水平较低。
虽然本研究结果表明所研究的代谢物与抑郁症之间存在关联，但不能得出因果关系的结论。本研究使用了最大的 MDE 患者样本，对血浆中外周色氨酸代谢进行了广泛评估。这些发现为 MDE 的外周特征提供了新的见解。这些变化的原因应进一步研究。这些结果可能提示新的抗抑郁治疗策略。
